1 INTERFERON RESPONSE IN COLOSTRUM-DEPRIVED NEWBORN CALVES INFECTED WITH BOVINE ROTAVIRUS : ITS POSSIBLE ROLE IN THE CONTROL OF THE PATHOGENICITY Catherine VANDEN BRŒCKE, Anne SCHWERS, Lise DAGENAIS, Anne GOOSSENS, Maria MAENHOUDT, P.-P. PASTORET, J. WERENNE To cite this version: Catherine VANDEN BRŒCKE, Anne SCHWERS, Lise DAGENAIS, Anne GOOSSENS, Maria MAENHOUDT, et al.. INTERFERON RESPONSE IN COLOSTRUM-DEPRIVED NEW- BORN CALVES INFECTED WITH BOVINE ROTAVIRUS : ITS POSSIBLE ROLE IN THE CONTROL OF THE PATHOGENICITY. Annales de Recherches Vétérinaires, 1984, 15 (1), pp <hal > HAL Id: hal https://hal.archives-ouvertes.fr/hal Submitted on 1 Jan 1984 HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
3 INTERFERON RESPONSE IN COLOSTRUM-DEPRIVED NEWBORN CALVES INFECTED WITH BOVINE ROTAVIRUS : ITS POSSIBLE ROLE IN THE CONTROL OF THE PATHOGENICITY Catherine VANDEN BRŒCKE 1 Anne SCHWERS 2 Lise DAGENAIS 2 Anne GOOSSENS Maria MAENHOUDT P.-P. PASTORET 2 J. 1WERENNE 1 : Department of General Chemistryl, Laboratory of Protein Chemistry, Faculty of Sciences, Free University of Brussels, 50, Avenuef. Roosevelt, B-1050 Brussels, Belgium 2: Department of Virology, Faculty of Veterinary Medicine, University of Lié ge, 45, rue des Vétérinaires, Brussels, Belgium Résumé INDUCTION D INTERFÉRON AU COURS DE L INFECTION DU VEAU NOUVEAU-NÉ PAR LE ROTAVI- RUS: RÔLE POSSIBLE DANS LE CONTRÔLE DE LA PATHOGÉNICITÉ. - Des veaux nouveau-nés privés de colostrum sont inoculés dès la naissance ou à l âge de trois jours au moyen de rotavirus produit en culture de cellules. La cinétique d apparition d interféron dans la circulation en réponse à différentes doses de virus est mise en corrélation avec l excrétion virale. Les fortes doses de virus conduisent à l induction précoce d interféron ; aucun symptôme clinique n est observé dans ces conditions. Aux faibles doses par contre, la production d interféron est beaucoup plus tardive; elle suit l apparition d une diarrhée intense mais de courte durée. Plusieurs vagues d induction sont observées dans tous les cas. Nos observations plaident en faveur du rôle de l interféron endogène dans la résistance du veau à l infection virale. Rotavirus is very often associated with neonatal calf diarrhoea (Pastoret and Schoenaers, 1977). It was shown recently to induce the production of interferon, both in the small intestine and in the serum of experimentally infected animals (La Bonnardidre et al., 1981 ). However, a functional role of interferon in the control of pathogenicity and in the recovery from rotaviral infection could not be ascribed from the available data. Colostrum-deprived newborn calves infected with high doses of cell culture rotavirus did not show any clinical symptom (Schwers et al., 1982), while calves inoculated with lower doses of the same virus isolate presented diarrhoea (Schwers et a/, 1983a). The virus produced in cell culture conserves therefore its pathogenicity for newborn calf. A possible explanation for the paradoxical dose effect observed in these experiments is a control of the viral pathogenicity by endogenous interferon. It was therefore essential to analyze interferon production after experimental rotavirus infection. The clinical and virological studies have been presented in a separate paper (Schwers et al., 1 983b). We report here the kinetics data concerning the interferon induction, in parallel with viral excretion, in eleven colostrum-deprived calves experimentally infected with different doses of bovine rotavirus. Materials and Methods Virus Bovine rotavirus strains S14 and S77, both isolated from stools of calves dead from diarrhoea (Dagenais et a/., 1981a), were used after four (S77) or six (S14) passages on GBK (Georgia Bovine Kidney) cells. Virus was titrated following the method of Matsuno et al. (1977).
4 Experimental procedure Eleven colostrum-deprived newborn calves were used in the experiments reported here. They were isolated immediately after birth in individual containers in thoroughly decontaminated stable and inoculated orally with different doses of one of the two rotavirus strains studied. The experimental procedure has been described in detail in a separate paper (Schwers et al., 1 983b) and is briefly summarized in figure 1. To allow direct correlation of the data, identical numbering of the calves is used in both papers. Plasma and stool samples were collected before and twice a day for at least ten days after inoculation; sera were taken on days 0 and 15. Virus isolation and counter-immuno-e%ctroosmophoresis (CIEOP) Virus isolation from stool samples have been performed for one sample per calf and per day, following the method of Babiuk et al. (1977). The CIEOP technique described by Middleton et al. (1976) has been used for detection of rotavirus antigen in stools and of antirotavirus antibodies in sera. Interferon titration The plasma were maintained at ― 85 C until interferon titration. The circulating interferon activity was determined in GBK cells, grown in MEM containing non essential amino-acids, penicillin, streptomycin and 10! foetal calf serum. The technique of reduction of cytopathic effect of VSV as challenge virus was used according to Stewart (1979). Results The kinetics of interferon response to experimental infection of newborn calves with rotavirus in different conditions were correlated with virus excretion in the faeces. They are schematically presented for all the calves studied in figure 1, and are detailed, for some of them, in figure 2. With a first group of animals (calves 1 to 5) receiving within two hours after birth high doses of rotavirus, a similar profile of interferon production was observed. An early peak of activity was detected beginning on day 1 after infection. After total clearance from the circulation, two other peaks of antiviral activity appeared around days 6 and 10. The different waves of interferon production correlate well with the periods of virus excretion. None of the animals of this group showed any sign of diarrhoea. In calves 7 and 8, inoculated 3 days after birth, a first peak of interferon production appeared in the circulation in less than 24 hours; the second wave of interferon production was delayed until day 9 to 12 (6 to 9 days after viral inoculation). The calves of this group did not show any symptom either. The third group of animals received immediately after birth a much lower dose of rotavirus 577: in this case, also multiple peaks of interferon activity appeared in the circulation. The antiviral activity reached a similar level with these virus doses as with the higher dose used before. The kinetics of interferon induction was however quite different : the antiviral activity did not appear before the third day of life. This delay of 24 to 48 h was observed for the three waves of interferon production. In these conditions, a severe but transient diarrhoea was observed 48 h after viral infection, before any interferon could be detected in the circulation. No sign of diarrhoea persisted at the time interferon appeared in the plasma. No other general symptom was observed. Finally (data not shown), an uninfected control calf (10), isolated in the same conditions, was also studied; a contact calf (9) not inoculated, but kept in the same stable as the infected calves 7 and 8, showed a very minor virus excretion at day 7 ; soft stools rich in mucus were observed from day 2 to day 4. In neither of these calves, was interferon detected. Discussion The data reported here indicate a possible role of interferon in the control of viral infections in the bovine species. Our results show that a threshold level of infecting virus is necessary to observe an early interferon response. With the lower dose of virus used here, the pathogenicity of the virus is expressed transiently. The replication of the virus occurs in the epithelial cells of duodenum and jejunum and (Mebus et al., 1971) interferon is subsequently produced. With very high doses of rotavirus (in fact much higher than what a calf may ingest in natural conditions), interferon is produced immediately and no symptoms were observed. However, using a sensitive ELISA test, La Bonnardiere et al. (1981) detected in young animals inoculated with bovine rotavirus a weak, but significant viraemia. Whether the interferon appearing in the circulation is produced by intestinal cells or induced in blood cells by these circulating viral antigens is not yet known and deserves further investigation. A mechanism of interference was suggested to explain the early and non-specific protection observed in calves after oral vaccination with an attenuated rotavirus strain (Mebus et al., 1972) and in mice successively inoculated with two different strains of rotavirus (La Bonnardi6re et al., 1979), but the induction of interferon has not been demonstrated in these conditions.
5 As interferon production in calves inoculated with high doses of virus is so early and so well correlated with virus excretion, our data are strongly indicative of a protection mediated by interferon. Moreover, if lower doses ofvirus are used, the interferon appears much later after the onset of diarrhoea, which stops when the level of antiviral activity becomes significant in the circulation. If this interpretation is correct, one should conclude that with a high dose of infecting virus, interferon is produced immediately when particles reach the target cells. With a lower virus dose, at least one multiplication cycle appears necessary before interferon could be significantly induced. During this later process, the pathogenicity is transiently expressed. The periodicity of interferon production results probably from the progression of the infectious process along the intestinal tract (Mebus et al., 1971) : the virus reaches regions where the antiviral state is not yet established. By infecting cells at these sites, a new wave of interferon production is observed, which limits the infectious process again. A similar process has recently been described in calves after experimental infection with bovine respiratory syncitial virus (El Azhary et a/., 1981). In this case however, interferon production could not be correlated with virus production. Our data indicate that interferon plays an important role in the resistance of the calf to viruses. It appears as a key factor in the natural recovery from viral infections; it may also block completely the development of symptoms. Such involvement of endogenous interferon in host resistance to various viral diseases has been directly demonstrated in the mouse by showing that anti-interferon antibodies increase mortality
6 (Fauconnier, 1971 ; Gresser et al., 1976 a,b). Moreover, interferon permits a limited multiplication of rotavirus, and seroconversion may appear (Schwers et al., 1983b). This observation indicates that interferon is able to protect an animal against viral infection without blocking the
7 establishment of the specific long term resistance mechanisms. The protection we report here is linked to the sensitivity of the rotavirus strains used (Dagenais et al., 1981b1. As La Bonnardi6re et al. (1980) reported a weak in vitro susceptibility of another rotavirus strain, our in vivo study should be extended before it could be generalized. However, as the multiplication in cell culture of Bovine herpesvirus 1 and Suid herpesvirus 1, two other economically important viruses, is inhibited by interferon (Goossens et al., 19831, we may expect that exogenous interferon will be active against many viral diseases in cattle. The recent demonstration of an efficient protection against experimental vaccinia infection using human interferon (Hu-IFNa2) (Werenne et ai., 1984) opens therefore interesting perpectives for interferon in veterinary medicine. Acknowledgements This work was supported in part by the I RSIA from which Catherine Vanden Broecke is a student fellow. Accepted for publication, 4th May 1983 Summary Colostrum-deprived newborn calves were experimentally infected with cell-culture rotavirus. A similar process of infection was observed when the animals were inoculated immediately after birth or at the age of three days, with a corresponding delay in the onset of virus excretion and interferon production in the later case. With high doses of virus, interferon was produced very early and no symptoms were observed. With lower doses of virus, interferon production was delayed and preceded by a severe but transient diarrhoea. In all cases, several waves of interferon production were observed. Our data indicate that interferon plays an important role in the control of viral diseases in calves and in their natural recovery. References BABIUK L.A., MOHAMMED K., SPENCE L., FAUVEL M., PETRO R., Rotavirus isolation and cultivation in the presence of trypsin. J. Clin. Microbiol, 6, DAGENAIS L., SCHWERS A., PASTORET P.-P., LEROY P., 1981a. Comparison of bovine rotavirus strains by plaque assay. Vet. Microbiol, 6, DAGENAIS L., PASTORET P.-P., VANDEN BRŒCKE C., WERENNE J., 1981b. Susceptibility of bovine rotavirus to interferon. Arch. Virol., 70, EL AZHARY M.A.S.Y., SILIM A., ROY R.S., Interferon, fluorescent antibody and neutralizing antibody responses in sera of calves inoculated with bovine respiratory syncytial virus. Am. J. Vet. Res., 42, FAUCONNIER B., Effect of anti-interferon serum on experimental viral pathogenicity in vivo, Pathol. Biol., 19, GOOSSENS A., SCHWERS A., VANDEN BRŒCKE C., DAGENAIS L., MAENHOUDT M., DUWYN R., VAN CAMP B., PASTORET P.-P., WERENNE J., Sensibilité des virus de la rhinotrachéite infectieuse bovine et de la maladie d Aujeszky A l interféron humain produit par des bact 6ries (Hu-IFNa2). Ann. M6d. V6t., 127, GRESSER I., TOVEY M., BANDU M.-T., MAURY C., BROUTY-BOYE D., 1976a. Role of interferon in the pathogenesis of virus disease in mice as demonstrated by the use of anti-interferon serum. I : Rapid evolution of EMC virus infection. J. Exp. Med., 144, GRESSER I., TOVEY M., MAURY C., BANDU M.-T., 1976b. Role of interferon in the pathogenesis of viral disease in mice as demonstrated by the use of anti-interferon serum II : Studies with Herpes Simplex, Maloney Sarcoma, Vesicular Stomatitis, Newcastle Disease and Influenza viruses. J. Exp. Med., 144, LA BONNARDIERE C., de VAUREIX C., In vitro interference between heterologous rotaviruses. Colloque: Entérites virales chez l homme et l animal INSERM, 90, LA BONNARDIERE C., de VAUREIX C., L HARIDON R., SCHERRER R., Weak susceptibility of rotavirus to bovine interferon in calf kidney cells. Arch. Virol, 64, LA BONNARDIERE C., COHEN J., CONTREPOIS M., Interferon activity in rotavirus infected newborn calves. Ann. Rech. Vet., 12, MATSUNO S., INOUYE S., KONO R., Plaque assay of neonatal calf diarrhoea virus and the neutralizing antibody in human sera. J. Clin. Microbiol., 5, 1-4. MEBUS C.A., STAIR E.L., UNDERDAHL N.R., TWIEHAUS M.J., Pathology of neonatal calf diarrhoea induced by a reo-like virus. Vet. Pathol., 8, MEBUS C.A., WHITE R.G., STAIR E.L., RHODES M,B&dquo; 1WIEHAUS M.J., Results of a field trial using a reo-like virus vaccine. Vet. Med. Small Anim. Clin., 67,
8 MIDDLETON P.J., PETRIC M., HEWITT C.M., SZYMANSKI M.T., TAM J.S., Counter-immuno-electroosmophoresis for the detection of infantile gastroenteritis virus (orbi group) antigen and antibody. J. Clin. Pathol., 29, PASTORET P.-P., SCHD=NAERS F., Les diarrh6es néonatales d origine virale chez le veau. Ann. MEd. Vc!t., 127, SCHWERS A., PASTORET P.-P., VANDEN BRa=CKE C., WERENNE J., DAGENAIS L., MAENHOUDT M., D IETEREN G., Absence de diarrhée chez des veaux privés de colostrum et infect6s des la naissance 5 I aide de fortes doses de rotavirus bovin de culture cellulaire. Ann. M!ct Vét., 126, SCHWERS A., VANDEN BR!CKE C., PASTORET P.-P., WERENNE J., DAGENAIS L., MAENHOUDT M., 1983a. Dose effect on experimental reproduction of rotavirus diarrhoea in colostrum-deprived newborn calves. Vet. Rec., 112, 250. SCHWERS A., PASTORET P.-P., MAENHOUDT M., DAGENAIS L., VANDEN BRCECKE C., GOOSSENS A., WERENNE J., 1983b. Tentative de reproduction expérimentale de la diarrhée rotavirus chez des veaux nouveau-n6s privés de colostrum. Ann. Rech. Vét., 14, STEWART 1 W.E., The interferon system, Springer Verlag, Vienna - New York. WERENNE J., GOOSSENS A., SCHWERS A., VANDEN BRD=CKE C., BUGYAKI L., MAENHOUDT M., PASTORET P.-P., Antiviral effect of bacterially produced human interferon (Hu-IFNa2) against experimental vaccinia infection in calves. Submitted for publication.
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Global Identity Management of Virtual Machines Based on Remote Secure Elements Hassane Aissaoui, P. Urien, Guy Pujolle To cite this version: Hassane Aissaoui, P. Urien, Guy Pujolle. Global Identity Management
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GDS Resource Record: Generalization of the Delegation Signer Model Gilles Guette, Bernard Cousin, David Fort To cite this version: Gilles Guette, Bernard Cousin, David Fort. GDS Resource Record: Generalization
Smart building : a new concept of engineering education curriculum Anne-Marie Jolly, Christophe Léger, Guy Lamarque To cite this version: Anne-Marie Jolly, Christophe Léger, Guy Lamarque. Smart building
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